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Coadministration of doxorubicin and etoposide loaded in camel milk phospholipids liposomes showed increased antitumor activity in a murine model.

Maswadeh HM, Aljarbou AN, Alorainy MS, Rahmani AH, Khan MA - Int J Nanomedicine (2015)

Bottom Line: Tumor-bearing mice treated with a combination of Dox and ETP loaded into CML-Lip showed increased survival and reduced tumor growth compared to other groups, including the combination of Dox and ETP in DPPC-Lip.Fibrosarcoma-bearing mice treated with a combination of free (Dox + ETP) showed much higher tumor growth compared to those groups treated with CML-Lip-(Dox + ETP) or DPPC-Lip-(Dox + ETP).Immunohistochemical study was also performed to show the expression of tumor-suppressor PTEN, and it was found that the tumor tissues from the group of mice treated with a combination of free (Dox + ETP) showed greater loss of cytoplasmic PTEN than tumor tissues obtained from the groups of mice treated with CML-Lip-(Dox + ETP) or DPPC-Lip-(Dox + ETP).

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, College of Pharmacy, Qassim University, Buraydah, Kingdom of Saudi Arabia.

ABSTRACT
Small unilamellar vesicles from camel milk phospholipids (CML) mixture or from 1,2 dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) were prepared, and anticancer drugs doxorubicin (Dox) or etoposide (ETP) were loaded. Liposomal formulations were used against fibrosarcoma in a murine model. Results showed a very high percentage of Dox encapsulation (~98%) in liposomes (Lip) prepared from CML-Lip or DPPC-Lip, whereas the percentage of encapsulations of ETP was on the lower side, 22% of CML-Lip and 18% for DPPC-Lip. Differential scanning calorimetry curves show that Dox enhances the lamellar formation in CML-Lip, whereas ETP enhances the nonlamellar formation. Differential scanning calorimetry curves also showed that the presence of Dox and ETP together into DPPC-Lip produced the interdigitation effect. The in vivo anticancer activity of liposomal formulations of Dox or ETP or a combination of both was assessed against benzopyrene (BAP)-induced fibrosarcoma in a murine model. Tumor-bearing mice treated with a combination of Dox and ETP loaded into CML-Lip showed increased survival and reduced tumor growth compared to other groups, including the combination of Dox and ETP in DPPC-Lip. Fibrosarcoma-bearing mice treated with a combination of free (Dox + ETP) showed much higher tumor growth compared to those groups treated with CML-Lip-(Dox + ETP) or DPPC-Lip-(Dox + ETP). Immunohistochemical study was also performed to show the expression of tumor-suppressor PTEN, and it was found that the tumor tissues from the group of mice treated with a combination of free (Dox + ETP) showed greater loss of cytoplasmic PTEN than tumor tissues obtained from the groups of mice treated with CML-Lip-(Dox + ETP) or DPPC-Lip-(Dox + ETP).

No MeSH data available.


Related in: MedlinePlus

DSC curves.Notes: DSC curves for (A) camel milk phospholipid mixture, (B) camel milk phospholipid mixture with doxorubicin 94:6 w/w, (C) camel milk phospholipid mixture with etoposide 94:6 w/w, (D) pure doxorubicin, and (E) pure etoposide.Abbreviation: DSC, differential scanning calorimetry.
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f3-ijn-10-2847: DSC curves.Notes: DSC curves for (A) camel milk phospholipid mixture, (B) camel milk phospholipid mixture with doxorubicin 94:6 w/w, (C) camel milk phospholipid mixture with etoposide 94:6 w/w, (D) pure doxorubicin, and (E) pure etoposide.Abbreviation: DSC, differential scanning calorimetry.

Mentions: Figure 3A shows the DSC curve for camel phospholipids mixture. The DSC curve shows that the first highest transition peak of this mixture was observed at 42°C. It represents the mixture of phosphatidylcoline, PE, phosphatidylinositol, and lysophosphatidylcholine phospholipids mainly present in camel milk. In our recent study, the identification of these phospholipids was done by gas chromatography-mass spectrometry and HPLC.28 Due to the presence of PE in CML mixture, a second and third peak were also observed at 118°C and 180°C, respectively. It is well known that natural PE is the most abundant lipid in cellular membranes and can form either lamellar or nonlamellar phases. The second broad curve started at 85°C and ended at 122°C, indicating that the liquid crystalline phase and the hexagonal phase (fully hydrated) of PE phospholipids coexist. Transition from liquid–crystalline phase of nonlamellar hexagonal phase transition temperature (Th) has a low entropy (ΔH) (Table 2). The third peak at 188°C represents the nonlamellar cubic phase (cubic formation) of camel milk PE phospholipids.


Coadministration of doxorubicin and etoposide loaded in camel milk phospholipids liposomes showed increased antitumor activity in a murine model.

Maswadeh HM, Aljarbou AN, Alorainy MS, Rahmani AH, Khan MA - Int J Nanomedicine (2015)

DSC curves.Notes: DSC curves for (A) camel milk phospholipid mixture, (B) camel milk phospholipid mixture with doxorubicin 94:6 w/w, (C) camel milk phospholipid mixture with etoposide 94:6 w/w, (D) pure doxorubicin, and (E) pure etoposide.Abbreviation: DSC, differential scanning calorimetry.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4403685&req=5

f3-ijn-10-2847: DSC curves.Notes: DSC curves for (A) camel milk phospholipid mixture, (B) camel milk phospholipid mixture with doxorubicin 94:6 w/w, (C) camel milk phospholipid mixture with etoposide 94:6 w/w, (D) pure doxorubicin, and (E) pure etoposide.Abbreviation: DSC, differential scanning calorimetry.
Mentions: Figure 3A shows the DSC curve for camel phospholipids mixture. The DSC curve shows that the first highest transition peak of this mixture was observed at 42°C. It represents the mixture of phosphatidylcoline, PE, phosphatidylinositol, and lysophosphatidylcholine phospholipids mainly present in camel milk. In our recent study, the identification of these phospholipids was done by gas chromatography-mass spectrometry and HPLC.28 Due to the presence of PE in CML mixture, a second and third peak were also observed at 118°C and 180°C, respectively. It is well known that natural PE is the most abundant lipid in cellular membranes and can form either lamellar or nonlamellar phases. The second broad curve started at 85°C and ended at 122°C, indicating that the liquid crystalline phase and the hexagonal phase (fully hydrated) of PE phospholipids coexist. Transition from liquid–crystalline phase of nonlamellar hexagonal phase transition temperature (Th) has a low entropy (ΔH) (Table 2). The third peak at 188°C represents the nonlamellar cubic phase (cubic formation) of camel milk PE phospholipids.

Bottom Line: Tumor-bearing mice treated with a combination of Dox and ETP loaded into CML-Lip showed increased survival and reduced tumor growth compared to other groups, including the combination of Dox and ETP in DPPC-Lip.Fibrosarcoma-bearing mice treated with a combination of free (Dox + ETP) showed much higher tumor growth compared to those groups treated with CML-Lip-(Dox + ETP) or DPPC-Lip-(Dox + ETP).Immunohistochemical study was also performed to show the expression of tumor-suppressor PTEN, and it was found that the tumor tissues from the group of mice treated with a combination of free (Dox + ETP) showed greater loss of cytoplasmic PTEN than tumor tissues obtained from the groups of mice treated with CML-Lip-(Dox + ETP) or DPPC-Lip-(Dox + ETP).

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, College of Pharmacy, Qassim University, Buraydah, Kingdom of Saudi Arabia.

ABSTRACT
Small unilamellar vesicles from camel milk phospholipids (CML) mixture or from 1,2 dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) were prepared, and anticancer drugs doxorubicin (Dox) or etoposide (ETP) were loaded. Liposomal formulations were used against fibrosarcoma in a murine model. Results showed a very high percentage of Dox encapsulation (~98%) in liposomes (Lip) prepared from CML-Lip or DPPC-Lip, whereas the percentage of encapsulations of ETP was on the lower side, 22% of CML-Lip and 18% for DPPC-Lip. Differential scanning calorimetry curves show that Dox enhances the lamellar formation in CML-Lip, whereas ETP enhances the nonlamellar formation. Differential scanning calorimetry curves also showed that the presence of Dox and ETP together into DPPC-Lip produced the interdigitation effect. The in vivo anticancer activity of liposomal formulations of Dox or ETP or a combination of both was assessed against benzopyrene (BAP)-induced fibrosarcoma in a murine model. Tumor-bearing mice treated with a combination of Dox and ETP loaded into CML-Lip showed increased survival and reduced tumor growth compared to other groups, including the combination of Dox and ETP in DPPC-Lip. Fibrosarcoma-bearing mice treated with a combination of free (Dox + ETP) showed much higher tumor growth compared to those groups treated with CML-Lip-(Dox + ETP) or DPPC-Lip-(Dox + ETP). Immunohistochemical study was also performed to show the expression of tumor-suppressor PTEN, and it was found that the tumor tissues from the group of mice treated with a combination of free (Dox + ETP) showed greater loss of cytoplasmic PTEN than tumor tissues obtained from the groups of mice treated with CML-Lip-(Dox + ETP) or DPPC-Lip-(Dox + ETP).

No MeSH data available.


Related in: MedlinePlus